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Increased IFRD1 Expression in Human Colon Cancers Predicts Reduced Patient Survival

机译:人性结肠癌中的IFRD1表达增加预测减少病人的生存

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Abstract Background Colon cancer (CRC) is the third most common cancer worldwide. CRC develops through combinations of genetic and epigenetic changes. However, there is marked heterogeneity in the “driver gene” mutational profiles within and among colon cancers from individual patients, and these are not sufficient to explain differences in colon cancer behavior and treatment response. Global modulation of the tumor landscape may play a role in cancer behavior. Interferon-related developmental regulator 1 (IFRD1) is a transcriptional co-regulator that modulates expression of large gene cassettes and plays a role in gut epithelial proliferation following massive intestinal resection. Aims We address the hypothesis that increased IFRD1 expression in colon cancers is associated with poorer patient survival. Methods Tumor and normal tissue from colon cancer patient cohorts from the USA, Spain, and China were used for this study. Cancers were scored for the intensity of IFRD1 immunostaining. The primary clinical outcome was overall survival defined as time from diagnosis to death due to cancer. Kaplan–Meier method and log-rank analysis were used to assess the association between IFRD1 expression and survival. Results Almost all (98.7%) colon cancers showed readily detectable IFRD1 expression, with immunoreactivity primarily in the tumor cytoplasm. High IFRD1 colon cancer expression was significantly associated with decreased 5-year patient survival. Patients in the American cohort with high IFRD1 expression had a poorer prognosis. Conclusions We have demonstrated that high IFRD1 protein expression in colon cancer is associated with poorer patient prognosis, suggesting a potential role for IFRD1 in modulating tumor behavior.
机译:摘要背景结肠癌(CRC)是全世界第三次常见的癌症。 CRC通过遗传和表观遗传变化的组合发展。然而,来自个体患者的结肠癌内部和结肠癌中的“司机基因”突变谱中有明显的异质性,这些患者不足以解释结肠癌行为和治疗反应的差异。全球调制肿瘤景观可能在癌症行为中发挥作用。与干扰素相关的发育调节剂1(IFRD1)是一种转录共调节剂,调节大型基因盒的表达,并在大规模肠道切除后在肠道上皮增殖中起作用。目的我们解决了结肠癌中的IFRD1表达增加的假设与较差的患者存活相关。方法采用美国,西班牙和中国的结肠癌患者群体中肿瘤和正常组织用于本研究。癌症被评分为IFRD1免疫染色的强度。主要临床结果是整体存活定义为因癌症而从诊断到死亡的时间。 Kaplan-Meier方法和日志秩分析用于评估IFRD1表达和生存之间的关联。结果几乎所有(98.7%)结肠癌显示出易于检测的IFRD1表达,主要在肿瘤细胞质中具有免疫反应性。高IFRD1结肠癌表达与5年的患者存活率下降显着相关。美国队列的患者高IFRD1表达的预后较差。结论我们已经证明,结肠癌的高IFRD1蛋白表达与较差的患者预后有关,表明IFRD1在调节肿瘤行为方面的潜在作用。

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